The study and prevention of Chronic Obstructive Pulmonary Disease (COPD) is seriously hampered by the difficulty of: 1) detecting pathologic lesions early in the course of disease, 2) correlating decrements in lung function with disease related changes in lung structure. The proposed research addresses these problems by aiming to develop a non-invasive in-vivo probe of pulmonary structure based on aerosol deposition measurements. Preliminary work has shown that aerosol deposition depends on details of pulmonary structure. Then a theoretical deposition model was fit to experimental data it produced values of alveolar size, total alveolar volume, alveolar duct size, total alveolar volume close to those seen in morphometric studies. Aerosol deposition measurements were also able to detect airspace enlargement in papain induced emphysema. A variation on the model directly predicts the mean linear intercept, a key morphometric parameter, related to both alveolar wall destruction and the total gas exchanging surface area of the lung. The proposed research will validate aerosol derived pulmonary dimensions by correlating them with morphometry is isolated lungs. We will determine the diameters of both alveoli and alveolar ducts and the total volumes they occupy. Non-parenchymal volume will be estimated from a two tired analysis of photomicrographs and gross sections. Morphometric measurement of the mean linear intercept will be compared directly with its determination by the aerosol probe. We will then apply the aerosol probe to follow emphysematous changes in the pulmonary structure of Jog lungs exposed to papain, both in-vivo and in-vitro. Elastic recoil and forced expiratory flow will also be measured. We hypothesize that for early or mild states of disease only aerosol deposition will be affected: whereas at later stages both aerosol deposition and functional tests will show abnormalities. The sensitivity of the method will be determined by morphometry on the lungs of dogs with mild disease, as indicated by the aerosol probe.